Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study.
Adult
Antibodies, Monoclonal
/ administration & dosage
Biomarkers
/ analysis
C-Reactive Protein
/ analysis
Colitis, Ulcerative
/ drug therapy
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Therapy, Combination
Endoscopy, Gastrointestinal
Feces
/ chemistry
Female
Gastrointestinal Agents
/ administration & dosage
Glucocorticoids
/ therapeutic use
Humans
Immunosuppressive Agents
/ therapeutic use
Leukocyte L1 Antigen Complex
/ analysis
Male
Portugal
Prospective Studies
Remission Induction
Golimumab
trough levels
ulcerative colitis
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
28 Oct 2019
28 Oct 2019
Historique:
pubmed:
17
4
2019
medline:
31
3
2020
entrez:
17
4
2019
Statut:
ppublish
Résumé
Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters.
METHODS
METHODS
This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6.
RESULTS
RESULTS
A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044].
CONCLUSIONS
CONCLUSIONS
A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.
Identifiants
pubmed: 30989180
pii: 5466449
doi: 10.1093/ecco-jcc/jjz071
doi:
Substances chimiques
Antibodies, Monoclonal
0
Biomarkers
0
Gastrointestinal Agents
0
Glucocorticoids
0
Immunosuppressive Agents
0
Leukocyte L1 Antigen Complex
0
C-Reactive Protein
9007-41-4
golimumab
91X1KLU43E
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1387-1393Informations de copyright
Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.